烟雾病合并动脉瘤一例

1 病例简介 　　患者男,43岁,农民,因"复视伴左上睑下垂7 d,加重1 d"于2007年3月14日入院. 　　患者于入院前7 d无明显诱因出现复视伴左上睑下垂,可睁眼,言语欠清,伴轻微头痛,无眩晕,无恶心呕吐,无肢体无力及抽搐,无意识障碍,1 d前左眼睁眼不能.入院前2个月突发失语伴右肢活动不良,在当地医院诊断为脑梗死,治疗后好转.否认高血压,糖尿病病史.……     

Genetic analysis of ring finger protein 213 (RNF213) c.14576G>A polymorphism in patients with vertebral artery dissection: a comparative study with moyamoya disease

ABSTRACT

Background: Intracranial vertebral artery dissection (VAD) and moyamoya disease (MMD) are rare cerebrovascular diseases, both of which have an ethnic predominance in the East Asian population. Disruption of the internal elastic lamina and subsequent rupture of the medial layer result in intracranial VAD. MMD is a chronic occlusive cerebrovascular disease of unknown etiology, in which the medial layer and internal elastic lamina of the intracranial arteries are significantly compromised. Recent genetic studies found ring finger protein 213 (RNF213) to be an important susceptibility gene for MMD in East Asian patients, but the association between VAD and RNF213 has not been investigated. .

Methods: We investigated polymorphism of the RNF213 gene (c.14576G>A) in genomic DNA of 24 patients with intracranial VAD in comparison with 58 patients with definitive MMD and 48 healthy controls.

Results: Although RNF213 gene polymorphism (c.14576G>A) was evident in 69% of the MMD patients (40/58), none of the patients with intracranial VAD had this characteristic polymorphism (0/24, p < 0.001). The incidence of RNF213 c.14576G>A polymorphism was 4.2% in healthy controls (2/48). After adjustment by age and sex, the incidence of RNF213 c.14576G>A was significantly lower in intracranial VAD patients (p = 0.021) than that in MMD patients.

Conclusions: In contrast to MMD patients, the prevalence of RNF213 c.14576G>A polymorphism was significantly lower in patients with intracranial VAD. The RNF213 gene polymorphism may preferentially affect the cerebrovascular lesion in the anterior circulation, which is originated from the primitive internal carotid arteries. The genetic background underlying intracranial VAD should be elucidated in future studies.

Abbreviations: VAD: vertebral artery dissection; MMD: moyamoya disease; RNF213: ring finger protein 213; CAD: carotid artery dissection     

单侧Moyamoya病合并动静脉畸形一例

1病例资料患者,女性,16岁,主因"突发头晕头痛7d"入院。7d前于活动中突发头晕头痛,伴恶心,呕吐,无视物模糊,无肢体麻木及运动障碍,于当地医院行颅脑CT示:左小脑半球及蚓部出血,四脑室无明显受压(图1),为进一步诊治来我院。     

Validation and Extension Study Exploring the Role of RNF213 p.R4810K in 2,877 Chinese Moyamoya Disease Patients

ObjectiveTo validate, update, and extend the role of RNF213 p.R4810K (G>A) for predicting the phenotype of moyamoya disease (MMD) patients and explore the different effects on pediatric and adult groups.MethodsA total of 2,877 patients conducted from 2004 to 2018 were included. Review Manage 5.3 and SPSS 20.0 were applied to complete all statistical analyses. Information on age at onset, sex, initial symptom, family history and complications were obtained via retrospective chart review. Angiographic records were evaluated.ResultsIn China, geographic proximity to Korea or Japan may affect the carrying rate of RNF213 p.R4810K. The proportion of patients with the following characteristics was significantly higher (P <0.017) in the GA than in the GG group: female, age at onset < 18 years, infarct after transient ischemic attack, family history of MMD, and posterior cerebral artery involvement. For pediatric patients, GA showed more cerebral hemorrhage (CH) (odds ratios (ORs) [95% confidence intervals (CIs)] = 3.99 (1.61-9.88), P = 0.003), more patients were in the Suzuki early and intermediate stage (P = 0.001; P = 0.001, respectively), while for the adult group, GA indicated more female (OR [95% CIs] = 1.43 [1.15-1.79], P = 0.001), fewer patients with diabetes (0.58 [0.38-0.86], P = 0.007) and intermediate Suzuki stage (P = 3.70 × 10⁻⁴).ConclusionsThe incidence and carrying rates of RNF213 p.R4810K in various regions for Chinese MMD patients were obviously different. RNF213 p.R4810K has different predictive effects on phenotypes of pediatric and adult patients.     

Reversible Cerebral Angiopathy after Viral Infection in a Pediatric Patient with Genetic Variant of RNF213

Ring finger protein (RNF) 213 is known as a susceptibility gene for moyamoya disease (MMD), which is characterized by bilateral carotid folk stenosis. Cerebral angiopathy after viral infection has been known to present angiographical appearance resembling MMD, however its pathogenesis and genetic background are not well known. We report a case of reversible cerebral angiopathy after viral infection in a pediatric patient with genetic variant of RNF213 mutation. The patient had developed a severe headache after hand, foot, and mouth disease. Magnetic resonance imaging and magnetic resonance angiography (MRA) performed 2-3 weeks after disease onset revealed bilateral carotid folk stenosis and an old cerebral infarction in the left putamen. The patient's headache spontaneously resolved and the follow-up MRA showed a complete spontaneous resolution of the arterial stenosis after 9 months. We were able to determine genetic predisposition to angiopathy by identifying the RNF213 c.14576G>A (rs112735431, p.R4859K) mutation. Based on the present case, we hypothesize that an RNF213 variant might play an important role for the onset of postviral cerebral angiopathy.     

Association of HLA-DR and -DQ Genes with Familial Moyamoya Disease in Koreans

Objective

Moyamoya disease (MMD) is an uncommon cerebrovascular disorder, characterized by progressive occlusion at the terminal portion of the internal carotid artery. Incidence of the disease is high in East Asia and familial MMD accounts for about 15% of the disease. Although the pathogenesis is unknown, association of HLA class I or II alleles with MMD has been reported with conflicting results. We investigated whether there is a difference in HLA class II association between familial and non-familial forms of the disease.

Methods

A total of 70 Korean children with MMD, including 16 familial cases (10 probands), and 207 healthy controls were studied. Among familial cases, only 10 probands were used for the HLA frequency analysis. High resolution HLA-DRB1 and DQB1 genotyping was performed using polymerase chain reaction (PCR)-sequence specific oligonucleotide hybridization and PCR-single strand conformation polymorphism methods.

Results

The phenotype frequencies of HLA-DRB1^*1302 (70.0%) and DQB1^*0609 (40.0%) were significantly increased in familial MMD compared to both controls [vs. 15.5%, corrected p (p_c) = 0.008, odds ratio (OR) = 12.76; vs. 4.3%, p_c = 0.02, OR = 14.67] and non-familial MMD patients (vs. 14.8%, p_c = 0.02, OR = 13.42; vs. 1.9%, p_c = 0.02, OR = 35.33). The frequencies of DRB1 and DQB1 alleles in non-familial MMD patients were not significantly different from those in controls.

Conclusion

Our findings suggest that the genetic polymorphism of HLA class II genes or other closely linked disease relevant gene(s) could be a genetic predisposing factor for familial MMD.     

Psychosocial Constructs Associated with Condom Use Among High-Risk African American Men Newly Diagnosed with a Sexually Transmitted Disease

Background  

African American men are disproportionately burdened by the US AIDS epidemic.     

Autism Spectrum Disorder Associated with 48,XXYY: Case Report of a Rare Clinical Syndrome

Journal of Autism and Developmental Disorders -     

Cognitive Decline in Patients with Familial Alzheimer's Disease Associated with E280a Presenilin-1 Mutation: A Longitudinal Study

Few longitudinal studies have been carried out to investigate the cognitive decline in early onset of familial Alzheimer's disease (FAD). In this study 12 patients with FAD (M age = 49.61 years, SD = 4.99), 10 patients with sporadic Alzheimer's disease (SAD) (M age = 71.40, SD =10.00), and 15 matched normal controls (M age = 45.01, SD = 7.24) were selected. A comprehensive neuropsychological battery was administered three times over a period of 18 months. Individuals designated as FAD met the criteria for dementia and were positive for the E280A presenilin 1 mutation. Participants with SAD met the criteria for dementia and were negative for the E280A presenilin 1 mutation. Normal control participants were the FAD patients' relatives, who were negative for the mutation. Two groups of neuropsychological instruments were administered: (1) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery, and (2) additional neuropsychological tests of ion and constructional abilities. Patients with FAD were significantly impaired on all measures at the first examination except for reading of words. While the performance of the normal controls remained unchanged over the 18 months for most neuropsychological tests, the patients with FAD displayed a decline in verbal memory, language, constructional and abstraction tests. The greatest decline was observed on the Mini-Mental State Exam scores. Patients with SAD demonstrated a similar pattern of cognitive decline, but the decline was faster in FAD than in SAD participants.     

烟雾病患者微栓子信号与临床表现及梗死灶关系的初步观察

目的 分析烟雾病患者的微栓子信号（microembolic signal,MES）与临床表现及梗死灶的关系。方法 总结了6例在常规经颅多普勒超声（transcranial Doppler,TCD）检查中出现MES的烟雾病患者的临床资料及弥散加权成像（diffusion-weighted imaging,DWI）影像资料,分析MES与患者临床表现及DWI上梗死灶之间的关系。结果 6例患者的MES均出现在大脑中动脉（middle cerebral artery,MCA）,3例（50%）闭塞,3例（50%）狭窄。6例中5例（83.33%）患者一个月内出现过缺血性症状,其中3例（50%）症状发生在无MES侧MCA供血区域;1例（16.67%）症状交替发生在MES同侧或对侧MCA供血区;1例（16.67%）为后循环缺血。5例（83.33%）患者DWI上出现梗死灶,在MES同侧MCA供血区内出现梗死灶的共有4（66.67%）例,无MES侧MCA供血区内出现梗死灶的共有5例（83.33%）。均为（100%）多发性梗死,皮层梗死为最常见梗死类型。结论 无论近期是否出现过缺血症状,烟雾病患者狭窄或闭塞的MCA均可发现MES。这些MES的存在与临床症状及梗死灶的相关性有待进一步研究。     

A Magnetic Resonance Angiography-Based Study Comparing Machine Learning and Clinical Evaluation: Screening Intracranial Regions Associated with the Hemorrhagic Stroke of Adult Moyamoya Disease

ObjectivesMoyamoya disease patients with hemorrhagic stroke usually have a poor prognosis. This study aimed to determine whether hemorrhagic moyamoya disease could be distinguished from MRA images using transfer deep learning and to screen potential regions that contain rich distinguishing information from MRA images in moyamoya disease.Materials and methodsA total of 116 adult patients with bilateral moyamoya diseases suffering from hemorrhagic or ischemia complications were retrospectively screened. Based on original MRA images at the level of the basal cistern, basal ganglia, and centrum semiovale, we adopted the pretrained ResNet18 to build three models for differentiating hemorrhagic moyamoya disease. Grad-CAM was applied to visualize the regions of interest.ResultsFor the test set, the accuracies of model differentiation in the basal cistern, basal ganglia, and centrum semiovale were 93.3%, 91.5%, and 86.4%, respectively. Visualization of the regions of interest demonstrated that the models focused on the deep and periventricular white matter and abnormal collateral vessels in hemorrhagic moyamoya disease.ConclusionA transfer learning model based on MRA images of the basal cistern and basal ganglia showed a good ability to differentiate between patients with hemorrhagic moyamoya disease and those with ischemic moyamoya disease. The deep and periventricular white matter and collateral vessels at the level of the basal cistern and basal ganglia may contain rich distinguishing information.     

Factors Associated with Discontinuation of Bupropion and Counseling Among African American Light Smokers in a Randomized Clinical Trial

Background

African Americans are at risk of inadequate adherence to smoking cessation treatment, yet little is known about what leads to treatment discontinuation.

Purpose

The purpose of this study was to examine the factors associated with discontinuation of treatment in African American light smokers (≤10 cigarettes per day).

Methods

Bupropion plasma levels and counseling attendance were measured among 540 African American light smokers in a placebo-controlled randomized trial of bupropion.

Results

By week 3, 28.0 % of subjects in the bupropion arm had discontinued bupropion, and only moderate associations were found between the plasma levels and self-reported bupropion use (r _s?=?0.38). By week 16, 36.9 % of all subjects had discontinued counseling. Males had greater odds of discontinuing medication (OR?=?2.02, 95% CI?=?1.10–3.71, p?=?0.02), and older adults had lower odds of discontinuing counseling (OR?=?0.96, 95% CI?=?0.94–0.97, p?<?0.0001).

Conclusions

Bupropion and smoking cessation counseling are underutilized even when provided within the context of a randomized trial. Future research is needed to examine strategies for improving treatment utilization among African American smokers. Trial Registration No. NCT00666978 (www.clinicaltrials.gov).